Psychosocial treatments for cocaine dependence: the role of depressive symptoms

Background

The association between cocaine use and depression has been frequently observed. However, less is known about the significance of depression in the treatment of cocaine use disorders. This study examined possible interrelations between drug use and depression severity among cocaine-dependent patients in psychosocial treatments for cocaine dependence.

Methods

Monthly assessed drug use and depression severity scores of N = 487 patients during 6-month psychosocial treatments for cocaine dependence were analyzed using hybrid latent growth models.

Results

Results indicated a moderate but statistically significant (z = 3.13, p < .01) influence of depression severity on increased drug use in the upcoming month, whereas drug use did not affect future depression severity.

Conclusions

Findings suggest that depression symptoms are an important predictor of drug use outcomes during psychosocial treatments for cocaine dependence and, hence, underline the importance of adequately addressing depression symptoms to improve treatment outcomes.     

5-HT induces temporomandibular joint nociception in rats through the local release of inflammatory mediators and activation of local β adrenoceptors

Objectives

The present studies assessed the effects of adolescent and adult ethanol exposure on the rewarding effects of cocaine as measured with the conditioned place preference procedure.

Methods

Male rats were exposed to intraperitoneal (IP) injections of ethanol or vehicle for 10 days [postnatal days (PNDs) 30-39 or PNDs 70-79; 2 mg/kg]. Place preference conditioning began on PND 65 or PND 105, respectively, and consisted of a baseline test followed by four conditioning cycles with either 0, 5, 10 or 20 mg/kg cocaine. Following the fourth conditioning cycle a final preference test was performed. Changes in time on the drug-paired side between the baseline and final test were analyzed.

Results

Animals exposed to vehicle (during adolescence or adulthood) showed a significant place preference at 20 mg/kg cocaine. Animals exposed to ethanol (during adolescence or adulthood) showed a significant place preference at 10 mg/kg cocaine.

Conclusions

Exposure to ethanol (adolescents or adults) sensitized the rewarding effects of cocaine. This may indicate an increase in the abuse liability of cocaine following a history of ethanol exposure.     

Exposure to alcohol during adolescence alters the aversive and locomotor-activating effects of cocaine in adult rats

Objectives

The present study assessed the effect of adolescent alcohol exposure on the later aversive and locomotor-activating effects of cocaine.

Methods

Male rats were exposed to alcohol or vehicle for 10 days [postnatal day (PND) 30-39; 2 g/kg IP]. Taste aversion conditioning began on PND 65. During aversion conditioning, subjects were presented with saccharin followed by cocaine (32 mg/kg; 15, 180 or 300 min post saccharin) or saline. Following each injection, animals were placed in locomotor chambers for 1 h. To determine if any effects seen were specific to the adolescent developmental period, the procedure was replicated in adult animals.

Results

Animals exposed to vehicle during adolescence showed significant aversions at all time delays. Animals exposed to ethanol during adolescence showed a decrease in consumption only at the 15 and 180 min delays. Groups exposed to alcohol during adolescence showed a decrease in gross, and an increase in fine, motor activity in response to cocaine. Animals exposed to alcohol during adulthood also showed attenuated taste aversions.

Conclusions

Exposure to ethanol during adolescence attenuated the aversive effects of cocaine and altered its locomotor-activating effects. Although this effect is not specific to adolescence, this is the time when alcohol use is typically initiated so that such exposure may enhance later abuse liability of cocaine.     

Prenatal cocaine exposure and small-for-gestational-age status: effects on growth at 6 years of age

Objective

To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.

Study design

Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.

Results

At birth cocaine-exposed infants (n = 364) had significantly lower growth parameters compared to non-exposed children (n = 771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).

Conclusions

Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.     

Gender, race, and group behavior in group drug treatment

Background

Group drug counseling is the primary treatment modality used to treat drug dependence in community settings in the United States. Findings from the social psychology literature suggest that gender may influence how individuals participate in groups, and that race may moderate the effects of gender on group behavior. This study examined gender, race, and their interaction as predictors of alliance, participation, self-disclosure, and receipt of advice and feedback in drug counseling groups, and explored how gender and racial differences in drug counseling group behavior related to outcome of cocaine dependence treatment.

Method

Ratings of group behavior were made from videotaped sessions of group drug counseling drawn from a randomized trial of treatment for cocaine-dependent individuals (n = 438). Analyses examined the effects of race (African American or non-Hispanic White), gender, and the race by gender interaction on group behavior. Additional analyses examined race, gender, and group behavior, and interactions among these variables in predicting monthly cocaine use.

Results

Race and the race by gender interaction, but not gender alone, predicted many group behaviors. Non-Hispanic White women had the highest rates of self-disclosure and receipt of advice and non-positive feedback, followed by men of both races, with African American women having the lowest levels. These differences were unrelated to cross-sectional cocaine outcome.

Conclusions

Women, but not men, of different races acted differently in mixed-race, mixed-gender cocaine treatment groups, with African American women exhibiting less of several behaviors. Additional research on causes and consequences of these differences could inform interventions for drug-dependent women.     

Violence among men and women in substance use disorder treatment: A multi-level event-based analysis

Background

This study examined associations between acute alcohol and drug use and violence towards others in conflict incidents (overall, partner, and non-partner conflict incidents) by men and women recruited from substance use disorder (SUD) treatment.

Methods

Semi-structured interviews were used to obtain details about interpersonal conflict incidents (substance use, whether specific conflicts were with intimate partners or non-partners) in the 180 days pre-treatment. Participants for this study were selected for screening positive for past-year violence (N = 160; 77% men, 23% women).

Results

Multi-level multinomial regression models showed that after adjusting for clustering within individual participants, the most consistent predictors of violence across models were acute cocaine use (significant for overall, intimate partner and non-partner models), acute heavy alcohol use (significant for overall and non-partner models), and male gender (significant in all models).

Conclusions

This study was the first to explicitly examine the role of acute alcohol and drug use across overall, partner and non-partner conflict incidents. Consistent with prior studies using a variety of methodologies, alcohol, cocaine use and male gender was most consistently and positively related to violence severity (e.g., resulting in injury). The results provide important and novel event-level information regarding the relationship between acute alcohol and specific drug use and the severity of violence in interpersonal conflict incidents.     

Social-environmental factors related to prenatal smoking

Introduction

Cigarette smoking during pregnancy is a significant public health issue that has profound effects on maternal and fetal health. Although many women stop smoking upon pregnancy recognition, a large number continue. Given the higher burden of smoking among low-income women, the focus of this study is to examine the impact of pre-conception social-environmental influences on smoking cessation during the first trimester of pregnancy.

Methods

Pregnant women who presented for prenatal were asked to complete a screening form at their first prenatal appointment. Women who agreed to participate were scheduled for a total of four interviews; a prenatal interview at the end of each trimester and a postnatal interview at 2 months of infant age. The sample for the current report consisted of pregnant women (first trimester) with a partner (N = 316).

Results

After controlling for pre-conception heaviness of smoking, a number of social-environmental factors were associated with smoking during the first trimester. Women were more likely to smoke during the first trimester if their partner was a smoker; however, the presence of other household smokers was not associated with increased risk for smoking. Additionally, women with a greater proportion of friends (but not relatives) who smoked and more frequent exposure to environmental tobacco were more likely to smoke.

Conclusions

This work found differential impacts of the social network on smoking suggesting that understanding relationship type, not simply number of smokers, may be important for smoking cessation efforts. Understanding differences in social network influences on smoking can help to inform interventions.     

Evaluation of the hydrolytic activity of a long-acting mutant bacterial cocaine in the presence of commonly co-administered drugs

Background

Cocaine toxicity is a prevalent problem in the Unites States for which there is currently no FDA-approved pharmacotherapy. We have developed a bacterial cocaine esterase (CocE) towards this indication. A thermostabilized mutant of CocE (DM-CocE) retains the hydrolytic activity of the wild-type esterase, rapidly hydrolyzing cocaine into the inactive metabolites ecgonine methyl ester and benzoic acid, and can prevent cocaine toxicities in rodent and non-human primate models. To advance DM-CocE towards clinical use, we examine here how the hydrolytic activity of DM-CocE is altered by some drugs commonly co-administered with cocaine.

Methods

We employed a spectrophotometric cocaine hydrolysis assay to evaluate whether pharmacologically relevant doses of alcohol, nicotine, morphine, phencyclidine, ketamine, methamphetamine, naltrexone, naloxone, or midazolam would alter the Michaelis-Menten kinetics of DM-CocE for cocaine. Mass spectrometry was used to evaluate interaction with diazepam as this drug interferes with the absorbance spectra of cocaine critical for the spectrophotometric assay.

Results

Alcohol, nicotine, morphine, phencyclidine, ketamine, methamphetamine, naltrexone, naloxone, and midazolam did not alter cocaine hydrolysis by DM-CocE. However, diazepam significantly slowed DM-CocE cocaine hydrolysis at very high concentrations, most likely through interaction of the phenyl ring of the benzodiazepine with the active site of DM-CocE.

Conclusions

DM-CocE does not display significant drug interactions, with the exception of diazepam, which may warrant further study as DM-CocE progresses towards a clinically used pharmacotherapy for cocaine toxicity. Alternate benzodiazepines, e.g., midazolam could be used to avoid this potential interaction.     

Rapid absorption of nicotine from new nicotine gum formulations

Rationale

A clinically limiting feature of currently-available nicotine gum is its slow rate of nicotine delivery and consequently slow onset of therapeutic effects. Previous research suggested that a nicotine hydrogen tartrate gum (NHTG1) that delivered nicotine more rapidly provided more effective craving relief. A subsequent gum formulation (NTHG2) was developed to further increase speed of delivery.

Objective

Compare the plasma nicotine absorption and clinical tolerability of NHTG2 to NHTG1 and Nicorette® FreshMint™.

Methods

A single-dose, randomized, crossover study evaluated the early kinetics of nicotine absorption and tolerability of 4 mg NHTG2 compared to NHTG1 and Nicorette.

Results

NHTG2 gum reached higher C_max (p = 0.059 versus Nicorette; p = 0.006 versus NHTG1) and delivered significantly more nicotine than Nicorette or NHTG1 within the first 10-30 min of chewing (AUCs_{0-10, 0-30}) and overall (AUC_0-180). NHT gums and Nicorette were well tolerated, with little difference in their AE profiles.

Conclusions

Study results indicate that NHTG2 gum provided more rapid uptake of nicotine in blood without notable decreases in tolerability. To the extent that rate of delivery and onset of therapeutic effects are related, these gums would be expected to provide more rapid therapeutic effects.     

Quetiapine improves response inhibition in alcohol dependent patients: a placebo-controlled pilot study

Rationale

Quetiapine has been shown to be a promising medication for the treatment of alcoholism. As an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT_1A and 5-HT_2A, H₁ and α1 and α2 receptors, quetiapine has been found to decrease impulsivity in other psychiatric disorders but its effects on impulsivity have not been studied in alcohol dependent patients.

Objective

This study seeks to test the effects of quetiapine on a specific dimension of impulsivity, namely response inhibition. This pilot study seeks to further elucidate the mechanisms of action of quetiapine for alcohol use disorders.

Method

A total of 20 non-treatment seeking alcohol dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants completed two counterbalanced intravenous placebo-alcohol administration sessions as well as behavioral measure of response inhibition (i.e. stop signal task) pre and post placebo-alcohol administration sessions.

Results

Analyses revealed a significant effect of quetiapine in improving response inhibition as measured by the stop signal task. These results provide preliminary evidence suggesting that quetiapine improves response inhibition in alcohol dependent patients, as compared to placebo.

Conclusion

This pilot study contributes a novel putative mechanism of action of quetiapine in alcoholism, namely an improvement in response inhibition.     

Cigarette smoking status in pathological gamblers: association with impulsivity and cognitive flexibility

Background

While the majority of pathological gamblers are current cigarette smokers (CS), some have quit smoking (former smokers, FS) while others never smoked (never smokers, NS). The reasons for elevated smoking rates in pathological gambling are not known, but gamblers may use nicotine as a putative cognitive enhancer. This study evaluated impulsivity and cognitive flexibility in a sample of pathological gamblers with differing smoking status.

Methods

Fifty-five subjects with pathological gambling (CS, n = 34; FS, n = 10; NS, n = 11) underwent cognitive assessments using the Stop-Signal (SST) and Intradimensional/Extra-dimensional (ID/ED) set-shift tasks.

Results

CS reported less severe gambling problems than either FS or NS on the Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling, and CS was associated with significantly fewer directional errors on the SST task, compared to NS. In addition, in CS, higher daily cigarette consumption was associated with fewer total errors on the ID/ED task.

Conclusions

The potential role of nicotine as a cognitive enhancer was supported by objective tests of impulsivity and cognitive flexibility. Human laboratory studies using nicotine challenges in pathological gambling will shed further light on this relationship.     

Regulation of cocaine self-administration in humans: Lack of evidence for loading and maintenance phases

Background

In rodents, cocaine self-administration under a fixed-ratio schedule and with timeout intervals limited to the duration of the infusions is characterized by an initial burst of drug intake (loading) followed by more stable infusion rates (maintenance). We sought to examine whether similar phases might characterize self-regulated cocaine use in humans.

Methods

31 Non-treatment seeking, cocaine dependent subjects participated in three (8, 16, and 32 mg/70 kg/infusion), self-regulated, 2-h cocaine self-administration sessions under a fixed-ratio 1, 5-min timeout schedule. Data were assessed for visual (e.g., by graphs of cumulative numbers of infusions) and statistical evidence of change in phase (by step-function analyses of individual infusion rates).

Results

Graphs of cumulative infusions over time suggested a single, linear rate of self-administration over 2 h at each cocaine dose. Statistical analyses of infusion data by generalized estimating equation (GEE) models also failed to support a loading/maintenance pattern (suggesting, if anything, the possibility of increasing infusion rates over time).

Conclusions

Our findings fail to support the existence of distinct loading and maintenance phases of self-regulated cocaine administration in humans at behaviorally relevant doses. Several factors may account for these observations including differences between humans and rodents in self-regulated drug intake.     

Executive dysfunction in chronic cocaine users: an exploratory study

Introduction

Chronic cocaine use is associated with some executive deficits. We assessed executive functions using ecologically valid tests in chronic cocaine users.

Objectives

To investigate the relationship between executive deficits and three measures of severity of cocaine use: years of use, quantity used, and frequency of use.

Methods

Twenty-four cocaine users were compared with twenty-seven community controls. We used Student's t-test and Chi-squared to compare means and categorical variables, respectively. Linear regression analyses for the adjusted comparative analysis between cases and controls, and severity of cocaine use among cocaine users were performed.

Results

Chronic cocaine users performed worse on measures of attention and working memory (Forward and Backward Digit Span, p < .001), set-shifting abilities (difference score between the Trail Making B and A, TMB-A, p = .006), cognitive test of mental flexibility and response inhibition (Rule Shift Cards) (p < .001), and prefrontal functioning (Wisconsin Card Sorting Test, WCST, p = .023) than controls. Years of cocaine use were associated with deficits in the Backward Digit Span (p = .041; CI 95%: −.760 to −.002), the TMB-A (p = .026; CI 95%: .687 to 9.761), the Zoo Map (p = .034; CI 95%: −.480 to −.021), and the Rule Shift Cards (p = .006; CI 95%: −.836 to −.164), among others. Quantity of cocaine use was associated with executive deficits measured by the Forward Digit Span (p = .007; CI 95%: −.727 to −.133), the TMB-A (p = .021; CI 95%: 5.304-57.945), and the number of perseverative errors in the WSCT (p = .002; CI 95%: −10.654 to −2.800). Frequency of cocaine was associated with deficits in the Backward Digit Span (p = .042; CI 95%: −1.548 to −.030).

Conclusions

Chronic use of cocaine is associated with executive deficits, which may influence patients’ functionality, prognosis, and therapeutic failure.     

Flunitrazepam in combination with alcohol engenders high levels of aggression in mice and rats

Rationale

Higher doses of benzodiazepines and alcohol induce sedation and sleep; however, in low to moderate doses these drugs can increase aggressive behavior.

Objectives

To assess firstly the effects of ethanol, secondly the effects of flunitrazepam, a so-called club drug, and thirdly the effects of flunitrazepam plus alcohol on aggression in mice and rats.

Methods

Exhaustive behavioral records of confrontations between a male resident and a male intruder were obtained twice a week, using CF-1 mice and Wistar rats. The salient aggressive and non-aggressive elements in the resident's repertoire were analyzed. Initially, the effects of ethanol (1.0 g/kg), and secondly flunitrazepam (0; 0.01; 0.1; and 0.3 mg/kg) were determined in all mice and rats; subsequently, flunitrazepam or vehicle, given intraperitoneally (0; 0.01; 0.1; and 0.3 mg/kg) was administered plus ethanol 1.0 g/kg or vehicle via gavage.

Results

The most significant finding is the escalation of aggression after a moderate dose of ethanol, and a low dose of flunitrazepam. The largest increase in aggressive behavior occurred after combined flunitrazepam plus ethanol treatment in mice and rats.

Conclusions

Ethanol can heighten aggressive behavior and flunitrazepam further increases this effect in male mice and rats.     

Contingency management with community reinforcement approach or twelve-step facilitation drug counseling for cocaine dependent pregnant women or women with young children

Background

Cocaine abuse among women of child-bearing years is a significant public health problem. This study evaluated the efficacy of contingency management (CM), the community reinforcement approach (CRA), and twelve-step facilitation (TSF) for cocaine-dependent pregnant women or women with young children.

Methods

Using a 2 × 2 study design, 145 cocaine dependent women were randomized to 24 weeks of CRA or TSF and to monetary vouchers provided contingent on cocaine-negative urine tests (CM) or non-contingently but yoked in value (voucher control, VC). Primary outcome measures included the longest consecutive period of documented abstinence, proportion of cocaine-negative urine tests (obtained twice-weekly), and percent days using cocaine (PDC) during treatment. Documented cocaine abstinence at baseline and 3, 6, 9 and 12 months following randomization was a secondary outcome.

Findings

CM was associated with significantly greater duration of cocaine abstinence (p < .01), higher proportion of cocaine-negative urine tests (p < 0.01), and higher proportion of documented abstinence across the 3-, 6-, 9- and 12-month assessments (p < 0.05), compared to VC. The differences between CRA and TSF were not significant for any of these measures (all p values ≥0.75). PDC decreased significantly from baseline during treatment in all four groups (p < 0.001) but did not differ significantly between CM and VC (p = 0.10) or between TSF and CRA (p = 0.23).

Interpretation

The study findings support the efficacy of CM for cocaine dependent pregnant women and women with young children but do not support greater efficacy of CRA compared to TSF or differential efficacy of CM when paired with either CRA or TSF.     

Validation of the Cannabis Expectancy Questionnaire (CEQ) in adult cannabis users in treatment

Background

Outcome expectancies are a key cognitive construct in the etiology, assessment and treatment of Substance Use Disorders. There is a research and clinical need for a cannabis expectancy measure validated in a clinical sample of cannabis users.

Method

The Cannabis Expectancy Questionnaire (CEQ) was subjected to exploratory (n = 501, mean age 27.45, 78% male) and confirmatory (n = 505, mean age 27.69, 78% male) factor analysis in two separate samples of cannabis users attending an outpatient cannabis treatment program. Weekly cannabis consumption was clinically assessed and patients completed the Severity of Dependence Scale-Cannabis (SDS-C) and the General Health Questionnaire (GHQ-28).

Results

Two factors representing Negative Cannabis Expectancies and Positive Cannabis Expectancies were identified. These provided a robust statistical and conceptual fit for the data. Internal reliabilities were high. Negative expectancies were associated with greater dependence severity (as measured by the SDS) and positive expectancies with higher consumption. The interaction of positive and negative expectancies was consistently significantly associated with self-reported functioning across all four GHQ-28 scales (Somatic Concerns, Anxiety, Social Dysfunction and Depression). Specifically, within the context of high positive cannabis expectancy, higher negative expectancy was predictive of more impaired functioning. By contrast, within the context of low positive cannabis expectancy, higher negative expectancy was predictive of better functioning.

Conclusions

The CEQ is the first cannabis expectancy measure to be validated in a sample of cannabis users in treatment. Negative and positive cannabis expectancy domains were uniquely associated with consumption, dependence severity and self-reported mental health functioning.     

Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: the dalcetrapib experience

Introduction

Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay.

Methods

Liver samples were obtained from ~ 1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored.

Results

Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5-1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250 mg/kg/day) to 160-fold (750 mg/kg/day), which declined slightly at 2000 mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750 mg/kg/day).

Discussion

These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay.     

A systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and health care utilization

Background

Alcohol use disorders (AUDs) are highly prevalent and associated with non-adherence to antiretroviral therapy, decreased health care utilization and poor HIV treatment outcomes among HIV-infected individuals.

Objectives

To systematically review studies assessing the impact of AUDs on: (1) medication adherence, (2) health care utilization and (3) biological treatment outcomes among people living with HIV/AIDS (PLWHA).

Data sources

Six electronic databases and Google Scholar were queried for articles published in English, French and Spanish from 1988 to 2010. Selected references from primary articles were also examined.

Review methods

Selection criteria included: (1) AUD and adherence (N = 20); (2) AUD and health services utilization (N = 11); or (3) AUD with CD4 count or HIV-1 RNA treatment outcomes (N = 10). Reviews, animal studies, non-peer reviewed documents and ongoing studies with unpublished data were excluded. Studies that did not differentiate HIV+ from HIV− status and those that did not distinguish between drug and alcohol use were also excluded. Data were extracted, appraised and summarized.

Data synthesis and conclusions

Our findings consistently support an association between AUDs and decreased adherence to antiretroviral therapy and poor HIV treatment outcomes among HIV-infected individuals. Their effect on health care utilization, however, was variable.     

A single-day paradigm of self-regulated human cocaine administration

Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs.

Methods

Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed.

Results

Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects (“high”) were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses.

Conclusions

These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).     

Cigarette, marijuana, and alcohol use and prior drug treatment among newly homeless young adults in New York City: Relationship to a history of foster care

Background

This study examined whether a history of foster care was associated with the risk for substance use among newly homeless young adults, controlling for demographics and other risk factors.

Methods

Multiple logistic regression analyses, adjusted for controls, among consecutive admissions of 424 newly homeless young adults (18-21 years), determined the association between foster care and substance use.

Results

A history of foster care was reported by 35% of the sample. Alcohol, marijuana, and cigarettes were the most frequently used substances. After adjusting for demographics, childhood emotional, physical, and sexual abuse, prior arrest, unemployment, lack of high school diploma, and family drug use, homeless young adults with histories of foster care were: three times as likely to smoke cigarettes (AOR = 3.09); more than three times as likely to use marijuana (AOR = 3.30); and almost nine times as likely to have been in drug treatment (AOR = 8.81) than those without such histories.

Conclusions

It is important to screen homeless young adults who exited foster care for substance use, particularly cigarettes and marijuana. Risk reduction interventions should be targeted and tailored to their substance prevention needs.